Many thanks, Cedric!

8/8 I appreciate that Caixia invited me to join this exciting scentific journey. This discovery was only possible through a team effort. Huge thanks and congrautulations to all collaborators!

7/8 Studying TranCs mirrors the classical framework of studying new gene origins: identify recent transitions, compare ancestral and derived states, infer key steps.

6/8 Why did Cas12 evolve repeatedly, while Cas9/Cas13 seemingly arose only once? We discuss that the huge diversity of TnpB transposons & the high evolvability of RNA created the perfect storm for recurrent origins, a potential case of molecular contingency.

5/8 We engineered this transition: by artificially splitting ISDra2 TnpB’s reRNA into tracrRNA and crRNA, we converted it into a functional CRISPR-like system. This confirms RNA splitting was a key step in Cas12 emergence.

4/8 Cryo-EM shows TranC (LaTranC) protein is structurally similar to its TnpB ancestor. The key innovation was at the RNA level: the guide reRNA functionally split into a tracrRNA & crRNA. Computional analysis indicate it as a convergent event across TranC clades.

3/8 These TranCs (e.g., LaTranC) are true intermediates: they can be guided by both CRISPR crRNAs AND transposon-derived reRNAs! This dual-guide capacity shows they retain ancestral TnpB function while acquiring CRISPR immunity.

2/8 Phylogenetic mining revealed several young Cas12 clades we call “TranCs”, i.e., nascent CRISPR systems emerging from distinct TnpB lineages. These represent multiple independent domestication events from transposons.